[Chronic hepatotoxicity evaluation of Chinese medicinal herb Zishen Yutai pill prepared from Polygoni Multiflori Radix preparata in dogs].

To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP) prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g·kg⁻¹; i.e. 3×, 6× and 12× equivalent doses) were given orally to dogs for 39 consecutive weeks. At the same time, the same volume of deionized water was used as the solvent control group, one time a day. The general condition of the animals was observed every day during the period of administration, and the blood was collected before and 13, 26, 39, 43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after 13, 39, and 43 weeks of administration to observe the pathological changes of the animal organs, weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group, 11 liver hepatotoxicity traditional biomarkers such as ALT, AST were found no ZYP-related changes at month 3, 6, 9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore, no obvious hepatotoxicity was shown by ZYP administered up to 6.0 g·kg⁻¹ for 9 months in normal dogs at doses of 1.5, 3.0, and 6.0 g·kg⁻¹.

Reproductive toxicity of ZishenYutai pill in rats: Perinatal and postnatal development study.

ZishenYutai pill (ZYP) is one of the most commonly used Chinese patent medicines for threatened miscarriage. Although ZYP is widely used, its toxic effects are rarely assessed. We aimed to investigate whether ZYP had reproductive toxicity during perinatal and postnatal period. Pregnant rats (F0) were continuously exposed to 6, 12 and 24 g/kg body weight/d of ZYP by intragastric administration from gestation day15 to post-natal day21. Vehicle and propylthiouracil (PTU, 15 mg/kg) were used as the negative control and positive control, respectively. The mating was done between the treatment (ZYP or PTU) group and negative control group when the F1 pups were born 63-70 days. Body weight, reproductive ability, physical development and neurodevelopment of F0, F1 and F2 pups were observed. The reproductive capacity of F0 and F1 generation decreased significantly after PTU exposure; however, the body weight and reproductive ability of F0, the physical development, weight, feed consumption and reproductive ability of F1, as well as the physical development and body weight of F2 rats were not significantly changed in the ZYP-treated group compared with the negative control group. ZYP exposure had no perinatal toxicity in 3 generations of rats and may be widely used for miscarriage.

Reproductive Toxicity of Zishen Yutai Pill in Rats: The Fertility and Early Embryonic Development Study (Segment I).

Purpose. This study was aimed to investigate the reproductive toxicity of Zishen Yutai Pill (ZYP) on fertility and early embryonic development in rats. Methods. SD rats were randomly divided into 5 groups: vehicle control group (distilled water, i.g.), positive control group (80 mg/kg of cyclophosphamide, i.p.), and three ZYP-treated groups (3, 6, and 12 g/kg/d, i.e., 12x, 24x, and 48x clinical doses, i.g.). The high dose was set as the maximum gavage dosage. Results. Cyclophosphamide showed diverse hazards, such as decreased weight of male reproductive organs and sperm density (P < 0.05). However, there were no obvious effects of ZYP on physical signs, animal behavior, and survival rate, as well as on weight and food intake during the premating and gestation periods. Importantly, there were no significant adverse effects of ZYP on indexes of copulation, fecundity and fertility indexes, weights and coefficients of male reproductive organs, epididymal sperm number and motility, estrous cycle, preimplantation loss rate, and implantation rate. Besides, the numbers of live and resorbed fetuses per litter were not significantly altered. Conclusions. ZYP had no reproductive toxicities on fertility and early embryonic development in rats at 48x equivalent clinical doses.